Speaker 1: The first hand account for this episode features the story
Speaker 1: involving the death of a family member. Some listeners might
Speaker 1: find this upsetting, so please listen with discretion.
Speaker 2: Hi. I'm Tori, and I have familial hypocholesterolemia. I think
Speaker 2: growing up, I always knew my dad was different because
Speaker 2: he walked with a limp and he spoke weirdly. He
Speaker 2: couldn't like write or do anything, but I didn't know why.
Speaker 2: And then I remember when I was ten years old,
Speaker 2: my mom requesting that I get my cholesterol checked at
Speaker 2: a doctor's appointment, and they're like, she's ten. I think
Speaker 2: it was when they sat me down and told me
Speaker 2: that my dad had had a heart attack which turned
Speaker 2: into a stroke when I was a baby, and so
Speaker 2: that's why things were a little different. And then that
Speaker 2: the same thing happened to his father. His father was
Speaker 2: forty five. My dad was forty seven when he had
Speaker 2: his heart attack, and then they told me what causes
Speaker 2: it and why they're worried that I could have it.
Speaker 2: When I was fourteen, my cholesterol was two hundred and
Speaker 2: thirty two, which not good, and they told me, like, oh,
Speaker 2: died an exercise. Come back in a year and it
Speaker 2: was two hundred and thirty one, and so we were like,
Speaker 2: this is something more, it's not just lifestyle. But then
Speaker 2: the pandemic happened and there was like so much going on.
Speaker 2: But I finally got like tested again, and they were like,
Speaker 2: we can't put you on statin unless you have a
Speaker 2: geneticist prove that this is something. So I had to
Speaker 2: go to a geneticist, and I have a fun little
Speaker 2: chart that's like she's missing something. That's now what I
Speaker 2: live with. I'm on statin for the past two years.
Speaker 2: My cholesterol is one ninety seven, still a little high.
Speaker 2: But last July, I was taking a nap and I
Speaker 2: got like shook away by my brother in law and
Speaker 2: I hear like sobbing in the background, and I remember
Speaker 2: being told we have to go to the hospital right now.
Speaker 2: And I check my phone and there's a text from
Speaker 2: my mom that says your sister's heart stopped and the
Speaker 2: name of the hospital that they were at. And so
Speaker 2: we speed over there, and when we get there, the
Speaker 2: chaplain tells us that there was nothing they could do.
Speaker 2: She was only three weeks away from her twenty sixth birthday.
Speaker 2: It was kind of a huge shock and kind of
Speaker 2: be like.
Speaker 3: Oh, this is real, This is like real real.
Speaker 2: You know. So, yeah, that's something that I live with
Speaker 2: and the constant back in my mind. I don't really
Speaker 2: know how to talk about it unless it's like fun
Speaker 2: fact my DNA's miss you know. But it always comes
Speaker 2: up where I'm like, oh, I don't eat red meat.
Speaker 3: Oh I can't have that.
Speaker 2: I can't do this. I have to take my pills.
Speaker 2: I have a plethora of pills that I take every
Speaker 2: morning a night. For a bit, my twin had to
Speaker 2: wear a heart monitor because they now have a FIB.
Speaker 2: I've dazzled it for them. It is something that's discussed openly.
Speaker 2: I think that fear has gotten really largely into my
Speaker 2: mom's head and she's like, you have to take this,
Speaker 2: this and this, and are you doing like your exercises
Speaker 2: and stuff like that, and so I think it is
Speaker 2: just very established that this is a fear. It's a
Speaker 2: huge part of my life, and then it's a huge
Speaker 2: part of my anxiety where it's like this could be it.
Speaker 3: But I think just realizing that.
Speaker 2: This is going to be the rest of my life
Speaker 2: and it may not be as long as you know,
Speaker 2: others and my dad was lucky to survive his heart attack.
Speaker 3: His father and my sister were not.
Speaker 2: So it's just kind of this like constant worry that
Speaker 2: this might happen, and a lot sooner than you think.
Speaker 1: Torri, thank you so much for taking the time to
Speaker 1: chat with us and share your story. We deeply, deeply
Speaker 1: appreciate it. Thank you so much. Hi, I'm Aaron Welsh
Speaker 1: and I'm Erin Alman Updike, And this is this podcast
Speaker 1: Will Kill You And.
Speaker 4: Today we're talking about cholesterol today and next week.
Speaker 3: Because it's kind of a big deal.
Speaker 5: So it's going to take a while.
Speaker 3: A pretty big deal. It's a pretty big deal.
Speaker 2: Yeah.
Speaker 1: We decided to divide this up into two different episodes
Speaker 1: because the first is really about cholesterol, because you know,
Speaker 1: LDL is one just one part of the cholesterol story.
Speaker 1: Athos Gloves is just one part of the story. And
Speaker 1: so that's the story that we're going to be talking
Speaker 1: about this week, So the role of cholesterol in our
Speaker 1: bodies overall and the role of cholesterol in disease. Yeah,
Speaker 1: and then next week we're talking statins, we're.
Speaker 5: Talking what do we do about it?
Speaker 3: What do we do about it?
Speaker 1: It won't it won't just be statins, but it will
Speaker 1: be focused on like how do we lower cholesterol? And
Speaker 1: why would we lower cholesterol?
Speaker 5: Why? Yeah? How low can we go? Just kidding that
Speaker 5: is like a very.
Speaker 1: Small part, but yeah, say there is a low that
Speaker 1: is too low?
Speaker 3: Correct?
Speaker 5: Yeah? Yes, yeah, do you eat it?
Speaker 1: There's there's a lot of good material to cover, so
Speaker 1: let's just get through the rest of this intro is necessary.
Speaker 1: It's not exciting, but like you know, we want to
Speaker 1: get to the media.
Speaker 3: It's quarantine disaster. What are we drinking this week?
Speaker 4: We're drinking plac attack black attack, black attack? Are we
Speaker 4: attacking plaque? Is plaque attacking us?
Speaker 5: A little bit of both?
Speaker 3: Yeah. Plac Attack is a delicious bev.
Speaker 1: It has blueberries and lemon juice and uh sparkling water
Speaker 1: and a little bit of simple syrup and cement to
Speaker 1: make it nice and refresh.
Speaker 2: Yeah.
Speaker 4: Has nothing to do with your cholesterol, but it is delicious.
Speaker 1: Yeah.
Speaker 4: We'll post the full recipe on our website, this podcast,
Speaker 4: Akillia dot com and all of our social media channels too.
Speaker 5: So are you following us there? Because then you could
Speaker 5: see this.
Speaker 3: You could see this, You could see this.
Speaker 1: You also could see this if you go to our
Speaker 1: website This podcast will Kill You dot com, which features
Speaker 1: not just pictures of quarantine, eat recipes and still maybe
Speaker 1: videos from past one's working on that still still, but
Speaker 1: you can also find things like transcripts. You can find
Speaker 1: our show notes. You can find links to bookshop dot org,
Speaker 1: affiliate page, music by Bloodmobile, about us page, merch Patreon,
Speaker 1: submit your first hand account form, contact us form.
Speaker 3: I got there in the end, you did.
Speaker 5: You really nailed it, are and I don't think you
Speaker 5: missed a single thing.
Speaker 3: Thanks for saying that. That's all we got, right.
Speaker 1: We can just yeah, I think so, rate reviews, subscribe,
Speaker 1: do those things, and also I'll just throw it out there,
Speaker 1: you know. Thank you to everyone who has ever suggested
Speaker 1: an episode topic.
Speaker 3: It's really helpful.
Speaker 1: We love getting topic ideas from you all and feedback
Speaker 1: from you all, and so keep it up.
Speaker 5: Yeah, I love it. Also, thank you to everyone who
Speaker 5: has submitted first hand accounts too. We really do read
Speaker 5: them all, and sometimes it might take us, like I
Speaker 5: don't know, two or three years.
Speaker 3: To reach out to you.
Speaker 1: That doesn't even longer us what our record is, yeah,
Speaker 1: more than three years, But.
Speaker 4: Thank you, we really do appreciate it. And like being
Speaker 4: able to hear all of your stories and share your stories.
Speaker 4: It's what makes this podcast in our opinions, So thank you.
Speaker 3: Absolutely.
Speaker 1: Well, let's take a quick break and then get into
Speaker 1: the story of cholesterol.
Speaker 4: Let's my goal for you today is that in the
Speaker 4: next I don't know twenty minutes or so, okay, you
Speaker 4: will understand what on earth cholesterol actually is and what
Speaker 4: our bodies are supposed to be using it for, and
Speaker 4: then what your doctor actually means when they talk about
Speaker 4: your quote unquote cholesterol and why those levels matter for
Speaker 4: your health.
Speaker 5: All right, love this, Okay.
Speaker 4: So, cholesterol itself is a type of lipid molecule, and
Speaker 4: we think of lipids as fats. Technically fats are just triglycerides,
Speaker 4: but whatever think of them as fats. And it's specifically
Speaker 4: a type of lipid called a sterol, like colsterolol.
Speaker 5: Okay.
Speaker 4: Cholesterol is just a string of carbons and hydrogens and
Speaker 4: one oxygen that's formed in these little rings. There's like
Speaker 4: four rings together, so it's a pretty rigid molecule. And
Speaker 4: cholesterol is an essential molecule for all animal life and
Speaker 4: really nearly all kinds of life on Earth need things
Speaker 4: like cholesterol. So plants they don't make cholesterol, really, but
Speaker 4: they do make a whole bunch of other very similar
Speaker 4: compounds called phytosterols phytosterols phytosterols. Anyway, all except booth thank you,
Speaker 4: and fungi make their cell membranes out of something called ergosterol. Okay,
Speaker 4: sterol also, And one of the biggest things that sterols,
Speaker 4: like cholesterol for us animals does is provide shape and
Speaker 4: structure to our cell membranes. So cholesterol molecules are interspersed
Speaker 4: throughout all of our cell membranes, like the outside of
Speaker 4: our cells, which is called our plasma membrane, and then
Speaker 4: also all of our organelles inside of our cells also
Speaker 4: have membranes that also have cholesterol within them. And what
Speaker 4: this does is provide just the right amount of rigidity
Speaker 4: and structure without being.
Speaker 5: Like too solid okay right.
Speaker 4: Cholesterol molecules are also moved back and forth across these
Speaker 4: cell membranes. They interact with proteins both inside and out
Speaker 4: side side membranes, and they serve as signaling molecules that
Speaker 4: helps our cells communicate like within the cells, like between organelles,
Speaker 4: and then also between cells themselves.
Speaker 2: Hmm.
Speaker 3: It's petra a big deal does a lot of things.
Speaker 4: It really does, because I'm not even done the backbone
Speaker 4: of cholesterol. Those ring structures of carbons and hydrogens are
Speaker 4: also the precursors to all of our steroid hormones. So
Speaker 4: that's estrogen, testosterone, cortisol, all of them, and vitamin D
Speaker 4: and our biol acids, which we learned in our gall
Speaker 4: butter episodes.
Speaker 5: Pretty freaking important.
Speaker 4: So suffice to say, we need cholesterol in order to
Speaker 4: be alive, right totally.
Speaker 5: Where do we get it from? Let me tell you.
Speaker 4: We make our own cholesterol, and most all of our
Speaker 4: cells can make cholesterol, like all of our cells are
Speaker 4: capable of it, but it's a pretty energy intensive process.
Speaker 5: So the vast.
Speaker 4: Majority of cholesterol that we actually use in our body
Speaker 4: is made in our liver.
Speaker 5: And then we also get.
Speaker 4: Cholesterol and other fats and fatty acids that we also
Speaker 4: need from our diet, so we absorb it through our
Speaker 4: intestine and then that gets transported to our liver. So
Speaker 4: while our cells can make their own cholesterol, they're generally
Speaker 4: not making quite enough of it, which is why our
Speaker 4: liver makes so much, something like more than fifty percent
Speaker 4: of the cholesterol that our cells use, which means that
Speaker 4: we have to be able to deliver cholesterol from our
Speaker 4: liver and our intestine to everywhere else in our body. Yea,
Speaker 4: and our body uses blood to transport stuff around, okay.
Speaker 3: The super high ways of the body exact.
Speaker 4: And so while cholesterol is integral to life, when it
Speaker 4: ends up causing problems, which is obviously what we're going
Speaker 4: to focus on for this episode, is when that cholesterol
Speaker 4: starts building up in high amounts in places that it shouldn't.
Speaker 4: That is where we can end up seeing cholesterol cause disease.
Speaker 4: And so to understand how that happens, we have to
Speaker 4: understand how it is that our body is moving cholesterol
Speaker 4: around from our liver to our cells, et cetera, and
Speaker 4: how our cells are cycling that cholesterol, because then we
Speaker 4: can understand how this might build up in places.
Speaker 5: That it shouldn't.
Speaker 4: Now, lipids, a key thing to understand about them, including
Speaker 4: cholesterol and all of our other fatty acids, is that
Speaker 4: they are not water soluble. Right, everyone who's tried to
Speaker 4: make salad dressing knows this, and what that means is
Speaker 4: that in order to move cholesterol around our bloodstream, it's
Speaker 4: not just going to be free floating because it won't
Speaker 4: do that well. Yes, So we actually move our cholesterol
Speaker 4: around our body in little packages called lipoproteins.
Speaker 3: Okay.
Speaker 4: Now we have a bunch of different kinds of LiPo proteins,
Speaker 4: lipofat protein, protein, and they all serve different functions. Most
Speaker 4: of our cholesterol is made in our liver, right, So
Speaker 4: our liver takes the cholesterol that it makes along with
Speaker 4: other fatty acids, and connects it to a protein and
Speaker 4: sends it out in a box that we call vl DL,
Speaker 4: or very low density lipoprotein. Right, So it sends that
Speaker 4: package out, and that is the type of cholesterol package
Speaker 4: that our cells are going to end up using. Along
Speaker 4: the way in our bloodstream. This VLDL gets broken down
Speaker 4: a bit and eventually becomes a smaller box of cholesterol
Speaker 4: and other fats that we call LDL or low density lipoproteink.
Speaker 4: So VLDL and LDL these are the lipoproteins. These are
Speaker 4: the packages of cholesterol that our cells are taking up
Speaker 4: and using for cholesterol.
Speaker 1: Okay, So these are the things that our liver is
Speaker 1: making to say, here you go. Here's you said you
Speaker 1: needed some cholesterol. To make your cell membranes or make
Speaker 1: some hormones or whatever. Here's this package starts out VLDL
Speaker 1: turns into LDL R.
Speaker 3: Cells take that up.
Speaker 4: Our cells are like, awesome, I got this. They grab
Speaker 4: onto it, They bring it inside of them, protein, cholesterol,
Speaker 4: fatty acids, and all in a little package right now.
Speaker 4: Once it's in our cells, our cells can either use
Speaker 4: it or they can store it for later if they're
Speaker 4: like I want to have a little extra, or they
Speaker 4: might get way too much of it, and then they
Speaker 4: have to send it back out into our bloodstream. When
Speaker 4: our cells are going to export extra cholesterol, they do
Speaker 4: it in a package called HDL or high density lipoprotein. Okay,
Speaker 4: And that is the cholesterol that's being transported from our
Speaker 4: cells back to our liver so that our liver can
Speaker 4: recycle it or excrete it into bile acids or whatever
Speaker 4: our liver's going to do with it.
Speaker 3: That makes sense.
Speaker 1: So this is LDL being the you know, quote unquote bad.
Speaker 4: Cholesterol unquote bad because this is what's going from our
Speaker 4: liver out to our cells floating around in our bloodstream.
Speaker 4: And it's small and it is sticky, so it can
Speaker 4: get stuck in places in our bloodstream, but it's also
Speaker 4: what our cells need to take it up and use it.
Speaker 4: And then HDL is what's going from ourselves back to
Speaker 4: our liver to be recycled.
Speaker 1: Okay, what's the relationship between maybe this is jumping ahead,
Speaker 1: give it, like the relationship between VLDL and LDL. What
Speaker 1: decides how much your liver is making? If high LDL
Speaker 1: is the problem, how does that? What's that feedback cycle?
Speaker 2: Like?
Speaker 4: Oh, this is really really good question, Aaron. The balance
Speaker 4: between how much of the different types of cholesterol packages
Speaker 4: that we have VLDL, LDL, HDL, whatever it is, It
Speaker 4: depends on a lot of different things. It depends on
Speaker 4: how much your liver is making, and some of that
Speaker 4: is just genetic. Some of that might have to do
Speaker 4: with your dietary factors. We know that like diets that
Speaker 4: are high in fat, especially saturated fat, increase the total
Speaker 4: amount of all these types of cholesterol in your bloodstream,
Speaker 4: all these different cholesterol packages. We don't know why, though.
Speaker 4: It also is going to depend on how good your
Speaker 4: cells are at taking this cholesterol out of your bloodstream.
Speaker 4: And one of the main things that determines that is
Speaker 4: how many what are called LDL receptors you have on
Speaker 4: your cells. These are like velcro myths that grab on
Speaker 4: to those LDL packages of cholesterol really efficiently and pull
Speaker 4: them into the cells so that those cells can use them.
Speaker 4: But if you don't have as many LDL receptors, or
Speaker 4: your LDL receptors are not as functional as someone else is,
Speaker 4: or they just get saturated because you end up with
Speaker 4: so much of that LDL cholesterol package floating around that
Speaker 4: all your receptors are full, then you're gonna have more
Speaker 4: of that LDL cholesterol in your body. And what determines
Speaker 4: how much HDL cholesterol you have is even more unknown
Speaker 4: because there's definitely like a big genetic factor there, but
Speaker 4: we don't know, like why is it that some people's
Speaker 4: cells are exporting more HDL and others aren't.
Speaker 1: And the VLDL LDL is just sort of like that's
Speaker 1: just a natural progression.
Speaker 3: It's a progression.
Speaker 4: Yeah, And again it is going to vary person to person,
Speaker 4: like how quickly that VLDL breaks down into LDL within
Speaker 4: your bloodstream while it's like bumping around. But it's all
Speaker 4: very like person dependent. There's not like a lot of.
Speaker 1: Hsiic is so it's so tricky because yeah, there are
Speaker 1: so many different drivers of LDL.
Speaker 3: Like why why?
Speaker 1: Okay, this is getting in a little bit to the
Speaker 1: evolution question of this, but like why would it be
Speaker 1: more beneficial to have more LDL receptors or fewer receptors?
Speaker 1: Why would it be better to store cholesterol rather than
Speaker 1: utilize it?
Speaker 5: Such great questions. I don't have answers.
Speaker 4: I had a feeling you were going to say, yeah,
Speaker 4: you know, I never do, but no, those are those
Speaker 4: are all really good questions because that is really the
Speaker 4: the determinant of whether cholesterol is going to become a
Speaker 4: problem is if it is building up in the wrong
Speaker 4: places or at the wrong times. And there are actually
Speaker 4: a whole bunch of diseases that I'm not going to
Speaker 4: get into any detail on today that are where cholesterol
Speaker 4: is building up not outside of ourselves, not in our
Speaker 4: bloods stream, but actually inside of our cells.
Speaker 5: So you can.
Speaker 4: Get build up of fats and cholesterol after that cholesterol
Speaker 4: has been taken up into our cells if you can't
Speaker 4: export it right. So for example, there's a genetic disorder
Speaker 4: called Niemen Pick disease. Okay, and this is where you
Speaker 4: have a defective basically exporter molecule, and so you would
Speaker 4: have really low HDL levels, low HDL levels and just
Speaker 4: low cholesterol levels overall because you're still taking up cholesterol
Speaker 4: from your bloodstream, but then you can't get rid of it,
Speaker 4: and now your cells are too full of cholesterol, right,
Speaker 4: so that's going to be really detrimental.
Speaker 3: There are other.
Speaker 4: Ones as well, and I'm not going to get into
Speaker 4: deep detail, because the way that we tend to worry
Speaker 4: about the build up of cholesterol for most people is
Speaker 4: when it builds up in our bloodstream, because that is
Speaker 4: when we see increased risk of a number of different diseases,
Speaker 4: but especially atherosclerosis, which is the fancy name for when
Speaker 4: cholesterol builds up in your blood vessels.
Speaker 1: Okay, so cholesterol meaning these packages, these LDL packages specifically.
Speaker 4: Well, yes, so here's what happens when you have high
Speaker 4: levels of these LDL packages, or not just LDL packages
Speaker 4: but other like VLDL, like other cholesterol packages that are
Speaker 4: not HDL. Okay, okay, non HDL cholesterol. If that's high
Speaker 4: levels in your bloodstream, then sometimes because many of those particles,
Speaker 4: especially LDL packages, are small and sticky in our blood vessels,
Speaker 4: especially maybe at say bifurcations, like somewhere where your blood
Speaker 4: vessels split or a curvature, or a place where you
Speaker 4: got damage for some reason or another. Those molecules can
Speaker 4: get stuck along the walls of our blood vessels and
Speaker 4: they get just underneath the first layer of cells into
Speaker 4: the wall of our blood vessel, and once they are there,
Speaker 4: those packages kind of disintegrate, and then you do have
Speaker 4: just free cholesterol molecules in the wall of our blood vessel,
Speaker 4: and our immune system is like, whoa dude, You're not
Speaker 4: supposed to be here. You're only supposed to be inside
Speaker 4: of cells or attached to your little protein package. What
Speaker 4: the heck are you doing here? So our immune system
Speaker 4: triggers a huge inflammatory response, and then that cycle basically
Speaker 4: can kind of continue. More cholesterol gets stuck because there's
Speaker 4: inflammation in the wall of your blood vessel. That triggers
Speaker 4: more inflammatory markers to come in, and then over time
Speaker 4: you get this build up of actual free cholesterol, not
Speaker 4: just these packages, but like cholesterol floating underneath the wall
Speaker 4: of your blood vessel. Okay, and then as these plaques
Speaker 4: build up and our body is trying to respond to it,
Speaker 4: eventually we build this kind of fibrous cap over it,
Speaker 4: our smooth muscle cells build a cap and eventually they calcify,
Speaker 4: and that's all our bodies response to try and stop
Speaker 4: this thing that's in the walls of our blood vessels
Speaker 4: from taking over essentially.
Speaker 1: Okay, so it's essentially a numbers game in that, you know,
Speaker 1: we can throw things like the LDAL receptors in there,
Speaker 1: we can throw, but ultimately it comes down to how
Speaker 1: much LDL is in your bloodstream that is not being
Speaker 1: taken up by cells for whatever reason, and that just
Speaker 1: is associated with more of these little clogs, these sort
Speaker 1: of sticking to the walls of your arteries, and then
Speaker 1: that cholesterol leaking out into the actual lining, causing inflammation
Speaker 1: and an immune response, which then leads to hard and plaques,
Speaker 1: et cetera, and problems down the line.
Speaker 4: Exact immediately yeah or immediately yeah. So those problems could
Speaker 4: be that the plaque gets so big that it actually
Speaker 4: blocks the vessel entirely, or it could be that the
Speaker 4: plaque gets big and then becomes unstable and a chunk
Speaker 4: of it breaks off, travels farther down and blocks smaller arteries. Okay, Okay,
Speaker 4: that's cholesterol and how it causes athrosclerosis as short as
Speaker 4: I could make it.
Speaker 1: Their tell me about the relationship between LDL and things
Speaker 1: like age.
Speaker 3: Things like diet.
Speaker 1: I know you mentioned saturated fats, but like and you said,
Speaker 1: we don't know the mechanism. And then also some hard
Speaker 1: numbers here, like what levels are we talking about and
Speaker 1: what is important to consider? Like what is that if
Speaker 1: you have a high LDL is that a snapshot in time?
Speaker 3: How long has.
Speaker 5: It been high?
Speaker 2: Oh?
Speaker 4: These are really fun questions. So yeah, in general, your
Speaker 4: total amount of cholesterol, and when we're measuring your total cholesterol,
Speaker 4: we're measuring all these different types of packages. Right, We're
Speaker 4: measuring the HDL packages, We're measuring the LDL packages, We're
Speaker 4: measuring all the packages. It is going to go up
Speaker 4: as we get older.
Speaker 5: Why, I don't know.
Speaker 4: Are is it because our LDL receptors that are taking
Speaker 4: this up are getting less efficient or not being recycled
Speaker 4: as easily. I don't have a perfect answer for you,
Speaker 4: but cholesterol does go up as we get older. So
Speaker 4: that is one of the biggest risk factors for atherosclerosis
Speaker 4: in general, is just age, and we can't do anything
Speaker 4: about that. You also asked about diet and other things
Speaker 4: that are going to influence it. Diet can have and
Speaker 4: not just diet, also like physical activity levels and what
Speaker 4: types of especially fat, so saturated fat versus unsaturated fat,
Speaker 4: versus dietary cholesterol versus how many carbohydrates you're getting. All
Speaker 4: of that is going to affect your body's cholesterol levels
Speaker 4: and all the different ratios of these different packages that
Speaker 4: we have. And we don't fully understand the exact mechanisms
Speaker 4: of how this happens, but what we do know is
Speaker 4: that diets that are higher in saturated fats tend to
Speaker 4: increase both your total amount of cholesterol and specifically your
Speaker 4: LDL cholesterol levels.
Speaker 5: Okay, but not your HDL cholesterol levels.
Speaker 1: Your body maintains a fairly consistent ability to produce HDL,
Speaker 1: and so HDL is independent of LDL levels.
Speaker 4: Yeah, okay, Yeah, they're not directly connected. There are things
Speaker 4: that you can do that will sort of shift their proportions, right.
Speaker 4: Increasing physical activity is actually one of those that ends
Speaker 4: up increasing the amount of HDL and lowering the amount
Speaker 4: of LDL, But there are lots of other things that
Speaker 4: might just affect one versus the other. HDL is one
Speaker 4: of the harder ones, because it's just really we don't
Speaker 4: fully understand, like how do we we know that having
Speaker 4: higher levels of HDL is protective against heart disease, right,
Speaker 4: but we don't know why exactly, We don't know exactly
Speaker 4: what levels it's at, and we don't really have a
Speaker 4: lot to do to try and increase somebody's HDL for example.
Speaker 5: Okay, is that interesting?
Speaker 4: And so go ahead, and you asked about hard numbers, yes, right, yes, yes, yes,
Speaker 4: Now these are going to depend a little bit on
Speaker 4: which guidelines that you're looking at and things like that.
Speaker 4: But like right now, the general can censis is that
Speaker 4: quote unquote ideal levels of LDL cholesterol would be less
Speaker 4: than one hundred milligrams per deestolator in your blood. Okay,
Speaker 4: does that mean that if you have more than one hundred,
Speaker 4: you're going to have plaque build up and you're going
Speaker 4: to have a high risk of heart attack? No, absolutely not.
Speaker 4: But we know that levels above a hundred are associated
Speaker 4: with higher risk than levels below one hundred, and we
Speaker 4: know that it's not quite like a linear relationship, but
Speaker 4: it is definitely an increasing risk with increasing LDL levels
Speaker 4: above one hundred. Yes, okay, So especially as those levels
Speaker 4: get to be above one hundred and sixty or one
Speaker 4: hundred and ninety milligrams per deestolator, then we are looking
Speaker 4: at that is considered a very high level of LDL
Speaker 4: in the bloodstream.
Speaker 3: Okay.
Speaker 4: And total cholesterol again, it's going to vary. Usually under
Speaker 4: two hundred or even under one hundred and sixty would
Speaker 4: be considered ideal total cholesterol. That's going to be again
Speaker 4: a measure of your LDLs, your HDLs, and all the
Speaker 4: other types of lipoprotein cholesterol packages.
Speaker 3: Okay, okay.
Speaker 1: And so when people talk about lifestyle modifications for managing
Speaker 1: cholesterol levels, is that mostly geared towards decreasing LDL with
Speaker 1: the kind of beneficial side effect of also hopefully increasing
Speaker 1: HDL if it's something like exercise or certain types of
Speaker 1: food that have an impact on both.
Speaker 4: That's exactly what it is. Yes, Yeah, it's all about
Speaker 4: dietary interventions, so decreasing saturated fats, increasing whole grains and
Speaker 4: plant based proteins that have higher amounts of unsaturated fats,
Speaker 4: and then increasing physical activity.
Speaker 2: Okay.
Speaker 4: Now, atherosclerosis or heart disease, cardiovascular disease, which are not
Speaker 4: all exactly the same thing, but I'm using them interchangeably.
Speaker 4: That is not the only thing that's associated with high
Speaker 4: levels of cholesterol or high levels of LDL cholesterol.
Speaker 2: Right.
Speaker 4: There are a lot of other things that are associated.
Speaker 4: And even when we hear the term cardiovascular, you might
Speaker 4: think that's only your heart, And yes, I'm talking about
Speaker 4: heart attack, I'm talking about heart disease, but I'm also
Speaker 4: talking about stroke. I'm also talking about chronic kidney disease,
Speaker 4: peripheral artery disease, and there's a whole range of other
Speaker 4: diseases that the more that we look for associations between
Speaker 4: high levels of LDL and other diseases, we find them
Speaker 4: liver disease. There's also strong associations between certain types of
Speaker 4: lipoproteins and an increased risk of Alzheimer's disease. And even
Speaker 4: though that's only like a strong association with one type
Speaker 4: of this like lipoprotein cholesterol package, it does look like
Speaker 4: lowering total amounts of LDL cholesterol can also lower the
Speaker 4: risk of Alzheimer's disease. Right, So there are these other associations.
Speaker 4: There's some thought that there's associations with cancer, and we
Speaker 4: just don't know the exact mechanisms.
Speaker 5: Of all of this.
Speaker 4: But high levels of LDL cholesterol are associated with this
Speaker 4: increased inflammatory response and this build up of cholesterol, especially
Speaker 4: in the arteries in your blood vessels. So that's cholesterol, Aaron,
Speaker 4: There's a lot more detail that I gotta be done.
Speaker 5: You know.
Speaker 3: It's a strange It's a strange beast. Yeah, yeah, yeah, So.
Speaker 5: Can you tell me? You know, I don't even know.
Speaker 5: I don't even know.
Speaker 1: You don't even know. You know, We'll find somewhere again.
Speaker 1: I think I can. I can make that happen. Cholesterol
Speaker 1: is vital. It is an essential part of all animal life.
Speaker 1: Without cholesterol, we wouldn't survive. Yet, these crucial functions have
Speaker 1: been overshadowed by its role in the development of cardiovascular disease.
Speaker 1: You could say that cholesterol is the Bill Buckner of
Speaker 1: cell biology.
Speaker 5: Bill Buckner.
Speaker 3: Do you know who that is?
Speaker 5: Why do I know that names?
Speaker 3: I'm so embarrassed.
Speaker 1: Okay, okay, okay, this basketball reference baseball. This might be
Speaker 1: a stretch, yeah, okay, But once I landed on it,
Speaker 1: I was like, I can't let this go.
Speaker 3: I'm going to force this analogy.
Speaker 1: Okay, So Buckner, Bill Buckner was a major League baseball player,
Speaker 1: really a well rounded player, had over twenty seven hundred
Speaker 1: hits in over his career, which spanned over twenty one seasons.
Speaker 3: Which is huge.
Speaker 1: Really, it was someone that you wanted on your team. Okay,
Speaker 1: great player. But in the nineteen eighty six World Series,
Speaker 1: while playing first base for the Red Sox, it was
Speaker 1: the bottom of the tenth inning and in Game six,
Speaker 1: and he missed a ground ball. It went right through
Speaker 1: his legs, brutal right. The error clinched the game for
Speaker 1: the Mets, and they went on to win the next game,
Speaker 1: making them World Series champs. And this is like Boston, right,
Speaker 1: So like Boston sports fans are known to be incredibly
Speaker 1: forgiving and understanding.
Speaker 3: They will never forget. Yeah. No, I think.
Speaker 1: After the Red Sox won in the two thousands, there
Speaker 1: was like, you know, okay, we forgive.
Speaker 3: You Bill Buckner type of a thing. But it only
Speaker 3: took almost twenty years.
Speaker 4: I have to know, Aarin, did you like already know
Speaker 4: this about Bill Buckner?
Speaker 1: How did you I have like I have felt so compassion,
Speaker 1: such compassion for Bill Buckner. I think I saw it
Speaker 1: on some sports special when I was like in high
Speaker 1: school or something, and I was just like, I was
Speaker 1: heartbroken because he was so reviled after this happened, and
Speaker 1: it was one mistake first of all, I mean, I
Speaker 1: could go into this. It was also like the pitchers
Speaker 1: had already blown the lead. It was game six, so
Speaker 1: they still had one more game that they could have won.
Speaker 1: But somehow all of this came down to Bill Buckner.
Speaker 5: You need it, you need a guy do you need Yeah?
Speaker 3: He was a scapegoat for sure.
Speaker 1: That's so that that missed ball, the Buckner play, it
Speaker 1: overshadowed his otherwise really impressive career, and it's mostly what
Speaker 1: he's known for. So Bill Buckner Cholesterol, same thing.
Speaker 2: Righting.
Speaker 1: Both you know, admirable should be appreciated for more than
Speaker 1: they are well rounded, but they're overshadowed by this bad reputation.
Speaker 1: The only difference between the two that I could descern
Speaker 1: is that Bill Buckner is undeserving of the hate that
Speaker 1: he got, whereas cholesterol has earned it's bad reputation, at
Speaker 1: least in certain contexts.
Speaker 5: I love this. This is the I will never forget
Speaker 5: this analogy is.
Speaker 3: So glad cholesterol and Bill Buckner.
Speaker 1: I don't think it's going to help anyone studying for
Speaker 1: a test, but hopefully it'll bring more appreciation for Bill Buckner. Okay, so,
Speaker 1: but today what I want to do is tell you
Speaker 1: how cholesterol earned this bad reputation. Our story begins around
Speaker 1: two and a half billion years ago with the Great
Speaker 1: Oxygenation Event.
Speaker 4: Oh, that's not the first time that we've gotten to
Speaker 4: start this podcast this way, and I just love it.
Speaker 3: It's it is.
Speaker 1: I'm like, man, I really we should just do an
Speaker 1: episode on that. I think it was our hemochromatosis episode
Speaker 1: when I talked about it in the Importance of Iron.
Speaker 3: Yeah, but it more recently.
Speaker 5: Yeah, don't know.
Speaker 2: Don't know.
Speaker 1: But what happened during the Great Oxygenation Event? There was
Speaker 1: a sharp sudden rise Booker.
Speaker 5: Was it Boogers?
Speaker 2: Oh?
Speaker 3: I think it was me. Might have been that sounds right.
Speaker 5: Yeah, I don't know.
Speaker 3: Sorry, whatever however it happened.
Speaker 1: But there was a sharp sudden rise in oxygen in
Speaker 1: the atmosphere that was caused by photosynthesizing cyanobacteria, and it
Speaker 1: had an enormous impact on life on this planet. Although
Speaker 1: we air breathers don't think of oxygen as harmful, it's
Speaker 1: actually quite toxic if you're not used to it, which
Speaker 1: at the time of the event described most of the
Speaker 1: anaerobes that were living on Earth, and so in response
Speaker 1: to the accumulating oxygen, many organisms died out like it
Speaker 1: was probably one of the greatest extinction events in our
Speaker 1: planet's history. But other organisms evolved mechanisms that protected them
Speaker 1: against oxidative damage, or they developed strategies to take advantage
Speaker 1: of this molecule. This new molecule, like, for instance, aerobic
Speaker 1: respiration cholesterol synthesis, which requires oxygen, evolved after the Great
Speaker 1: Oxygenation Event, and it dramatically changed things. So you you
Speaker 1: touched on this a bit, but in those early eukaryotes,
Speaker 1: cholesterol was incorporated into cell membranes, which made for more
Speaker 1: stable and less permeable barriers, protected them from oxydative stress,
Speaker 1: It allowed them to signal across cells within cells, and
Speaker 1: it just kind of helped to organize things, which ultimately
Speaker 1: allowed for greater complexity, even multicellularity, because then you're having like, oh,
Speaker 1: here's a little organelle that I can have, here's a
Speaker 1: little whatever. You're not doing open floor concept anymore. We
Speaker 1: are walling off, walling ourselves off.
Speaker 3: Off.
Speaker 1: So now establishing that so now fast forwarding to humans.
Speaker 1: By the time that our species came onto the scene,
Speaker 1: cholesterol synthesis had been around for billions of years, and
Speaker 1: the uses of cholesterol had expanded, became a precursor for
Speaker 1: hormones involved in stress reproduction metabolism. It was essential for
Speaker 1: staying warm as temperatures drop, and helped to provide enough
Speaker 1: energy for foraging. It was involved a lot in energy balance,
Speaker 1: and we weren't just making it ourselves. We were also
Speaker 1: getting it from our diet, which helped to free up
Speaker 1: energy that could be used for cognitive processing and social behavior.
Speaker 1: Being able to hold on to cholesterol that we got
Speaker 1: in our diets was really beneficial, particularly because food could
Speaker 1: become scarce, and so in some populations living in certain
Speaker 1: environments and under certain food availabilities, traits emerged that altered
Speaker 1: the ways that our bodies dealt with cholesterol. So, for instance,
Speaker 1: it's thought that like being able to utilize fats rapidly
Speaker 1: and efficiently would have been really helpful in cold environments
Speaker 1: when you needed to keep yourself warm and have enough
Speaker 1: energy for foraging, and so there might have been a
Speaker 1: particular pattern of cholesterol regulation that emerged in the people
Speaker 1: living under these conditions interesting, right, And so it's sort
Speaker 1: of thought that, like the way today that we regulate
Speaker 1: cholesterol would have been very helpful in the past, but
Speaker 1: in today's context, it's not really serving us well, right,
Speaker 1: faced with these same challenges most of the time.
Speaker 4: Well, and we just also have exposure to much higher
Speaker 4: levels of dietary facts and things that we would not
Speaker 4: have had exposure to thousands, hundreds of thousands of years ago, exactly.
Speaker 1: Yeah, yeah, And so it's again sort of like this
Speaker 1: context specific, something that evolved that was really beneficial under
Speaker 1: one context in modern times maybe isn't as much, you know,
Speaker 1: much much of the world lives a sedentary lifestyle and
Speaker 1: consumes a diet rich in animal fats, saturated fats, and sugars,
Speaker 1: where these types of foods are the ones that are
Speaker 1: the most readily available. And so given that the most
Speaker 1: damaging impacts of high cholesterol tend to happen later in
Speaker 1: our life, things like heart attack and stroke, it's not
Speaker 1: really surprising that high cholesterol seems to be a problem
Speaker 1: for so many of us, right, It's just the sort
Speaker 1: of constellation of different factors going on, right. But again,
Speaker 1: our relationship with cholesterol. You can't really paint it with
Speaker 1: a broad brush. It's super complicated, both at a population
Speaker 1: level as well as an individual level. Context really does
Speaker 1: matter with cholesterol, and this rich inner life of cholesterol
Speaker 1: is what makes it so challenging to understand and to
Speaker 1: communicate its health impacts. As important as cholesterol is in
Speaker 1: maintaining healthy physiology, it's also responsible for some major issues
Speaker 1: and scientists have suspected this darker side of cholesterol for
Speaker 1: over a century. Wow yeah, So since its discovery in
Speaker 1: the late seventeen hundreds and it's naming in eighteen fifteen cholesterol.
Speaker 3: Yeah, quite a long time. Yeah yeah.
Speaker 1: Cholesterol has inspired a great deal of fascination and over
Speaker 1: a dozen scientists have been awarded a Nobel Prize for
Speaker 1: their research on cholesterol.
Speaker 3: Wow. Yeah, just for gold mine. It really is.
Speaker 1: Yeah, In case you were curious, cholesterol comes from cholesterine,
Speaker 1: which was the name given to it in eighteen fifteen
Speaker 1: by Michelle Chevroule, who had isolated the stuff from human gallstones.
Speaker 1: So coal, like chol e is bile and stereo solid
Speaker 1: solid bile. Okaying, So when did people start to suspect
Speaker 1: cholesterol's role in atherosclerosis? The first clue that we have
Speaker 1: comes from nineteen ten, with a paper by German chemist A.
Speaker 1: Windaus reporting that his patients with atherosclerosis in autopsies, he
Speaker 1: found that their aortas were just chock full of cholesterol like,
Speaker 1: much more so than his patients who did not have
Speaker 1: the disease. The second clue arrives a few years later
Speaker 1: in nineteen thirteen, when Russian experimental pathologist A. Nichkow showed
Speaker 1: that when he fed rabbits basically pure cholesterol dissolved in
Speaker 1: sunflower oil, they quickly developed lesions in their blood vessels
Speaker 1: that looked a whole lot like human athrosclerosis. The rabbits
Speaker 1: who were fed on a normal diet did not develop
Speaker 1: those same lesions.
Speaker 3: Curious, very curious.
Speaker 1: And he was inspired to do this not because of
Speaker 1: Windows's paper, but because of other previous work investigating whether
Speaker 1: too much protein was toxic and caused premature aging. Interesting, yeah,
Speaker 1: which was kind of the idea at the time. And
Speaker 1: so there were these studies where rabbits were fed on
Speaker 1: a super protein rich diet and the rabbits developed what
Speaker 1: looked like human athrosclerosis, and so Innichkow wanted to know
Speaker 1: what it was was it the protein? Was what is
Speaker 1: it about the protein or that diet specifically that caused
Speaker 1: a lesions? And so he narrowed it down to cholesterol.
Speaker 1: H Yeah, fascinating. Yeah, and so on the surface and
Speaker 1: Nichkow's results showing that a diet high in cholesterol led
Speaker 1: to atherosclerosis like lesions, that's pretty compelling stuff to our
Speaker 1: modern eyes. Yeah, in reality, it did not resonate with
Speaker 1: the scientific community of the time.
Speaker 5: It never does, does it.
Speaker 3: It never does.
Speaker 1: That's okay, you know, like there were three main reasons
Speaker 1: for this hesitance.
Speaker 5: Okay.
Speaker 1: So the first was that when other people tried to
Speaker 1: replicate his results in different animals, no, dice wasn't happening.
Speaker 5: Okay.
Speaker 1: Even when a Nichkow himself tried with a dog, he
Speaker 1: could not produce a lesions, And so he reasoned that
Speaker 1: it might be because dogs, as omnivores, are more accustomed
Speaker 1: to eating cholesterol rich diets and so have evolved to
Speaker 1: excrete or convert excess cholesterol. Oh.
Speaker 3: Interesting, It turned out to be right about that way.
Speaker 1: Rabbits, being herbivores, don't have that same cholesterol, right, They're.
Speaker 4: Not usually eating cholesterol. So they're not equipped to manage it.
Speaker 1: Yeah, but I don't think other people made this connection,
Speaker 1: and so they were like, just I think it's just
Speaker 1: something about these rabbits, because I think.
Speaker 3: They also couldn't do it, and other animals like rats
Speaker 3: maybe anyway, Okay.
Speaker 1: What they were missing also was that this was a
Speaker 1: two stage process. You had to have a high cholesterol
Speaker 1: diet followed by a corresponding rise in blood cholesterol levels
Speaker 1: to get athrosclerosis.
Speaker 3: If you didn't have.
Speaker 1: That second step, if your diet was super high in
Speaker 1: cholesterol but you didn't actually have high circulating blood cholesterol,
Speaker 1: then you athroschlorosis probably wasn't going to develop because you
Speaker 1: were lacking the little the ability to make those platka.
Speaker 5: You ate it, but then it didn't get stuck in
Speaker 5: your blood.
Speaker 3: Did you get stuck?
Speaker 5: I never made it there for one reason, somehow.
Speaker 1: Excreted or processed in a different way, never absorbed it whatever, whatever.
Speaker 5: Just really groady poops, ye.
Speaker 3: Real rough, real rough.
Speaker 1: But the second reason that his results were met with
Speaker 1: skepticism was the blood cholesterol levels that he was inducing
Speaker 1: in these rabbits were staggering. It was like five hundred
Speaker 1: to one thousand milligrams pertest leader and above of total
Speaker 1: total cholesterol. Yeah, which is like way higher than it
Speaker 1: then it gets for most humans.
Speaker 4: Yeah, if I saw that, I would be when I
Speaker 4: get to the three hundreds, I'm.
Speaker 5: Like, we need to do something, thank you.
Speaker 3: Oh just wait till later.
Speaker 5: I don't know if it case episode or next.
Speaker 1: But but so it was kind of like, uh, well, yeah,
Speaker 1: enough of anything is deadly.
Speaker 3: But like that's just not realistic. We're not this is
Speaker 3: not what we're seeing.
Speaker 1: Later, though, he showed that even small rises, so not
Speaker 1: not five hundred to one thousand range, but like small
Speaker 1: rises still led to athroosclerosis like lesions in these rabbits,
Speaker 1: just longer to develop than like the couple of weeks
Speaker 1: or whatever it was.
Speaker 3: And then one last thing, the third.
Speaker 1: Thing that held him back was the prevailing view of
Speaker 1: athrosclerosis at the time when his work was being published.
Speaker 1: Athrosclerosis was seen as an inevitable part of the aging process, interesting,
Speaker 1: something that took decades to develop. And so how on
Speaker 1: earth could these rabbits showing these atherosclerotic lesions within months
Speaker 1: or weeks of eating lots of cholesterol. How could that
Speaker 1: be a reasonable model for human disease. It just didn't
Speaker 1: seem plausible.
Speaker 5: Doesn't make sense.
Speaker 2: Yeah.
Speaker 1: Interesting that skeptical sentiment followed A. Nichkow for decades as
Speaker 1: the sinescence hypothesis of athosclerosis proved particularly stubborn to dislodge
Speaker 1: for his part, and Nichkow pursued this line of research
Speaker 1: for fifty years. Like he was like singularly focused on,
Speaker 1: like I want to understand cholesterol and what's going on
Speaker 1: here till the end of his career.
Speaker 3: And I just wrote this little comment here.
Speaker 1: I wonder too, whether global politics came into play, because
Speaker 1: there's like Cold War stuff. He was friends with Stalin apparently,
Speaker 1: and so I'm wondering if there was just sort of
Speaker 1: like a well, we're gonna distrust.
Speaker 5: You, right, You're not a person that we want to
Speaker 5: hear from.
Speaker 3: Yeah.
Speaker 1: Yeah, I don't know. I didn't see that anywhere. That
Speaker 1: was just my own, my own little speculation. But in
Speaker 1: any case, the next phase of the cholesterol athrosclerosis story
Speaker 1: brings us to UC Berkeley in the mid twentieth century.
Speaker 5: Oh wow, A long time later.
Speaker 1: Yeah, yeah, about forty forty years or so.
Speaker 3: Fifty years Okay.
Speaker 1: Yeah, so there, young physician scientist John Goffman found himself
Speaker 1: drawn to cardiovascular disease, in particular the relationship between diet
Speaker 1: blood cholesterol and athrosclerosis, and he had come across in
Speaker 1: Nichkow's work, but rather than dismissing it like so many
Speaker 1: other people, he suspected that there might be something to
Speaker 1: the cholesterol athrosculerosis link. God, it's so hard to say
Speaker 1: that over and over again, but to get at the
Speaker 1: heart of that link. But I'm pun intended, I literally
Speaker 1: wrote pun intended. He nothing better than a planned joke.
Speaker 1: But he he was like, well, I have to better
Speaker 1: understand the dynamics of cholesterol in the blood, because by
Speaker 1: this point in time, researchers had recognized that there were
Speaker 1: these these compounds called lipoproteins that circulated in the blood.
Speaker 1: They carried cholesterol, and they came in different forms. So
Speaker 1: he was like, there might be like this, We can't
Speaker 1: just say cholesterol. We have to be more detailed than
Speaker 1: not to understand what's going on.
Speaker 5: Which cholesterol package are we talking?
Speaker 3: Yeah, exactly.
Speaker 1: And so people had recognized different lipoproteins, but they didn't
Speaker 1: know what they did and how their concentrations affected health.
Speaker 1: Interesting unclear okay. Gosman was really the first to clarify
Speaker 1: their role, and he did this through a complicated and
Speaker 1: sophisticated technique. The long and the short of it is
Speaker 1: that he was able to take a sample and reliably
Speaker 1: sort and measure the different types of lipoproteins in a
Speaker 1: blood And when he applied this technique to the question
Speaker 1: that interested him the most, what caused atherosclerosis, he found
Speaker 1: that not all lipoproteins had the same impact. And he
Speaker 1: proposed that we shouldn't be looking at total cholesterol. That's
Speaker 1: an incomplete picture. That's too broad of a picture. Really,
Speaker 1: you need to give different weight to the different lipoproteins
Speaker 1: in predicting the risk of cardiovascular disease. So, in other words,
Speaker 1: he came up with the athrogenic index. He was like,
Speaker 1: we need to we need to figure this out and
Speaker 1: have these specific numbers. And he applied this index to
Speaker 1: a small sample of patients and he showed that there
Speaker 1: was a strong association between certain ratios of lipoproteins and
Speaker 1: the risk of heart attack. As a fun little side here,
Speaker 1: his wife, doctor Helen Goffman, published what was probably the
Speaker 1: first heart healthy cookbook in nineteen fifty one, I think
Speaker 1: because of this research was like, Wow, don't eat saturated vats.
Speaker 1: Basically Goffman's research, though, really transformed the field. He bears
Speaker 1: the title the father of clinical lipidology.
Speaker 5: Wow, I know, gotta love it. Gotta love it when
Speaker 5: we get a father.
Speaker 1: Yeah, we have another father in the next episode, the
Speaker 1: father of statn's. Yeah. But his central hypothesis, linking certain
Speaker 1: cholesterol carrying lipoproteins with heart disease, once again, it met
Speaker 1: with resistance, understandably so to a degree. So first of all,
Speaker 1: he didn't have a mechanistic explanation as to why this
Speaker 1: would cause disease. That would have to wait for a
Speaker 1: few decades. And secondly, his sample sizes were fairly small.
Speaker 1: They weren't perspective, meaning you couldn't draw firm conclusions about causality,
Speaker 1: like which came first? Was it cholesterol or heart disease?
Speaker 5: Did you have heart disease and.
Speaker 1: That is what caused your high cholesterol? Righte So doubt
Speaker 1: lingered and things were getting heated. The quote unquote cholesterol
Speaker 1: wars that began in the nineteen fifties reached new heights
Speaker 1: in the nineteen seventies. Oh yeah, cholesterol Wars decades.
Speaker 5: More than Salt Wars.
Speaker 1: Honestly, very like, I would say, more contentious than Salt Wars.
Speaker 1: Interesting in my reading of it. Yeah, tell me all
Speaker 1: about it, Eric, Yeah.
Speaker 3: Okay.
Speaker 1: So, while some physicians and scientists had grown convinced.
Speaker 3: That high blood cholesterol caused heart.
Speaker 1: Disease, others argued that it was the other way around,
Speaker 1: and they took issue with high Where do you draw
Speaker 1: the line?
Speaker 3: What does high mean?
Speaker 5: Okay?
Speaker 3: Yeah, yeah, okay.
Speaker 1: So in medicine, one common cutoff for deciding this is
Speaker 1: ninety five percent. So, for example, if ninety five percent
Speaker 1: of people have cholesterol less than a particular value, anything
Speaker 1: above that is considered abnormal. The problem with this is
Speaker 1: that you're assuming any cholesterol value less than ninety five
Speaker 1: percent is normal. It's non pathogenic. But average doesn't always
Speaker 1: equate to normal. In the nineteen forties, ninety five percent
Speaker 1: of the US population had blood cholesterol below.
Speaker 5: To eighty to eighty to eighty ninety.
Speaker 1: We know today that, yeah, that heart attacks occur with
Speaker 1: levels much lower than that. In fact, most occur between
Speaker 1: two hundred and to eighty, But since that was the
Speaker 1: standard cut off at the time, doctors didn't consider a
Speaker 1: cholesterol level of say two fifty to be worrisome because
Speaker 1: it was considered normal.
Speaker 3: And this is total cholesterol. There's still total cholesterol.
Speaker 1: Yes, Yes, It took several strong epidemiological studies to turn
Speaker 1: that thinking around and say, like, actually, average does always
Speaker 1: equate to healthy.
Speaker 5: Yeah.
Speaker 1: So one of these studies I actually touched on in
Speaker 1: a previous episode our Dietary Guidelines episode canceled Keys's seven
Speaker 1: Countries study.
Speaker 3: So in the nineteen fifties.
Speaker 1: As a refresher, Keys and his colleagues conducted a wide
Speaker 1: ranging study across seven countries examining relationships between diet, blood cholesterol,
Speaker 1: and mortality due to coronary heart disease. The results were striking.
Speaker 1: At one end of the spectrum, you had Japan with
Speaker 1: an average blood cholesterol level of one sixty and less
Speaker 1: than five fatal heart attacks per one thousand men.
Speaker 3: Okay.
Speaker 1: On the other end, you've got Finland with an average
Speaker 1: blood cholesterol of two sixty and seventy fatal heart attacks
Speaker 1: per one thousand. Yeah, and other countries kind of followed
Speaker 1: the same trend, just like fell right on along that
Speaker 1: plot line with blood cholesterol and saturated fat consumption. Positively
Speaker 1: related to fatal heart attacks. Yep, again it was compelling stuff,
Speaker 1: but again, like in many other studies, it showed correlation
Speaker 1: and it didn't prove causation, and so a lot of
Speaker 1: people remained unconvinced. The next study turned all but the
Speaker 1: most stubborn skeptics into believers.
Speaker 5: Okay.
Speaker 1: In nineteen fifty researchers enrolled twenty eight thousand residents of Framingham, Massachusetts.
Speaker 5: Love it framing Ham, Framingham.
Speaker 1: The Framingham Study is one of the most It is
Speaker 1: one of the most long term and valuable and informative
Speaker 1: public health studies ever put together.
Speaker 3: It's incredible. It's incredible.
Speaker 1: They measured things like blood cholesterol, blood pressure, smoking, diabetes,
Speaker 1: and family history of disease, and they follow these residents
Speaker 1: for years. It is still ongoing, recording any disease events
Speaker 1: as they occurred.
Speaker 4: Including in offspring now the old offspring Like it's it
Speaker 4: is a huge de type of study that's been on
Speaker 4: going for so long.
Speaker 1: The amount of information we've gained really cool, really yeah powerful, Okay,
Speaker 1: But what this allowed them to do, what the study
Speaker 1: allowed them to do was establish a sequence high cholesterol
Speaker 1: preceded heart attack, and then they could also calculate risk.
Speaker 1: What is high cholesterol? How much does smoking combined.
Speaker 3: With high cholesterol impact risk? Things like that.
Speaker 1: They could create these sort of calculations and say, what
Speaker 1: are the factors that increases your risk of heart attack
Speaker 1: or stroke. Where the Seven Country study showed the relationship
Speaker 1: between blood cholesterol and heart disease at a population level,
Speaker 1: the Framingham Heart study demonstrated it in the individual. So
Speaker 1: this person had high cholesterol and then they experienced a
Speaker 1: heart attack. That was sort of that directional relationship, right.
Speaker 1: The link between high cholesterol and coronary heart disease could
Speaker 1: not be ignored.
Speaker 3: No no, which of course didn't prevent people from doing so.
Speaker 3: The wars continued.
Speaker 1: Aaron Wow, but increasingly those cholesterol doubters were becoming a
Speaker 1: tiny but vocal minority. Other studies, such as dietary intervention
Speaker 1: studies helped to build the case against cholesterol. But there
Speaker 1: was still one important facet missing, and that was a mechanism.
Speaker 1: So since at least the late eighteen hundreds, physicians had
Speaker 1: noticed a condition that ran in some families where people
Speaker 1: developed large deposits of lipids under their skin. Members of
Speaker 1: these families were very prone to develop severe cardiovascular disease
Speaker 1: at early ages, with some experiencing heart attacks in the
Speaker 1: first ten years of life, and by the early nineteen seventies,
Speaker 1: researchers had established that very high blood cholesterol was a
Speaker 1: key feature of this, hence the name familial hypercholesterol aemia,
Speaker 1: but they weren't sure what caused it or it it's
Speaker 1: role in disease development. Particularly, they were like, Okay, there's
Speaker 1: clearly a genetic link, but like, what's the mechanism here?
Speaker 1: What is that mutation that leads to these high cholesterol levels?
Speaker 4: Exactly what is going on that is causing this person's
Speaker 4: cholesterol to be so high and then resulting in all
Speaker 4: negative health outcomes?
Speaker 3: Like what's why? Why? Why why?
Speaker 1: In nineteen seventy three, the key to the puzzle was
Speaker 1: unlocked by two researchers, Michael Brown and Joseph Goldstein, who,
Speaker 1: over the course of their fifty year collaboration, would be
Speaker 1: compared to Rogers and Hammerstein, which is, so I love.
Speaker 5: That, yeah, Aaron, can we work together?
Speaker 3: Yes? Yes? I was like, can that be us? I
Speaker 3: want that to be us?
Speaker 5: Yes.
Speaker 4: I don't think we'll ever create something as good as
Speaker 4: Rogers and Hammerstein, though let's be let's be the ld Goldstein. Yes.
Speaker 1: Yeah. But Brown and Goldstein they were fascinated by the
Speaker 1: mystery of familial hypercholesterolemia and they wanted to figure out
Speaker 1: what caused such high levels of LDL and the blood
Speaker 1: in affected individuals, because that was really one of the
Speaker 1: key features of this was high LDL. As they discovered,
Speaker 1: it wasn't that there was too much LDL being produced,
Speaker 1: it was that too little LDL. It was being taken
Speaker 1: up by the cells.
Speaker 5: Ah, I love this so much, darn.
Speaker 1: So the cells of people with familial hypercholesterolemia lacked receptors
Speaker 1: that would allow them to scoop up the LDL from
Speaker 1: the bloodstream. So they didn't have those little velcrow hands, right,
Speaker 1: they didn't have enough felcrow hands, and so LDL just
Speaker 1: kept piling up, piling up, circulating and circulating with nowhere
Speaker 1: to go, and over time it just again it's a
Speaker 1: numbers game. It's going to lodge into the blood vessel walls.
Speaker 1: It's going to cause a blockage, inflammation, plaques, et cetera,
Speaker 1: et cetera.
Speaker 3: Huh.
Speaker 1: Yeah, this discovery, Brown and Goldstein's discovery of the ld receptor.
Speaker 3: It transformed the field wow, so much so.
Speaker 1: That it earned them a Nobel Prize in nineteen eighty five,
Speaker 1: because not only did it explain why people with familial
Speaker 1: hypercholesterolmia develop cardiovascular disease, it clarified how our cells regulate cholesterol,
Speaker 1: specifically LDL, and why disease happens when that regulation goes awry.
Speaker 1: So it was a major major step forward in solidifying
Speaker 1: the cholesterol heart disease link, and it opened these different
Speaker 1: pathways to treatment. Can we do something about this receptor
Speaker 1: right instance?
Speaker 3: Yeaheah.
Speaker 1: Did it end the cholesterol wars? Not necessarily, It really didn't.
Speaker 1: The debate continued, but it had lost a lot of steam.
Speaker 1: The advent of cholesterol lowering drugs like statins changed the
Speaker 1: conversation by turning cardiovascular disease from a disease to manage
Speaker 1: into one to treat, even prevent potentially. But as we'll
Speaker 1: see next week, their use has also been met with
Speaker 1: a hefty amount of skepticism, and so the cholesterol wars
Speaker 1: really continue through today.
Speaker 4: It is so interesting, Aaron, how much like it. It
Speaker 4: is really hard, I think to find someone who doesn't
Speaker 4: at least agree that high levels of cholesterol puts you
Speaker 4: at high risk for heart disease. Yeah, and yet and
Speaker 4: there still is so much, like mama, about what you
Speaker 4: do about it or what we shouldn't do about it,
Speaker 4: or what your diet effect might be.
Speaker 5: Like it's oh, I can't wait for next week.
Speaker 1: Yeah, there's there's a lot more to cover next week
Speaker 1: when it comes to the story of statins and how
Speaker 1: the role that they have played in changing our approach
Speaker 1: to managing and preventing heart disease. Also how the HECTU
Speaker 1: statins work. Do you want to know the answers to
Speaker 1: these questions?
Speaker 3: I want to tell you to turn in next week.
Speaker 4: Shall we tell people if they want to just learn
Speaker 4: more about what we've already talked.
Speaker 3: About, Yes, absolutely we should. I have a lot of
Speaker 3: sources for.
Speaker 5: This that you do erin.
Speaker 3: I'm shouting out.
Speaker 1: So there was a if you wanted to learn more
Speaker 1: about sort of cholesterol in oxygen and the Great oxygenation
Speaker 1: event and why it plays a role. There's a paper
Speaker 1: called the evolution of cholesterol rich membrane as oxygen adaptation
Speaker 1: the respiratory system as a model by Zuniga, Hertz and Patel.
Speaker 3: From twenty nineteen.
Speaker 1: I liked that one, and then there's an excellent series
Speaker 1: by Steinberg from two thousand and four. It's a five
Speaker 1: part series called an Interpretive History of the Cholesterol Controversy
Speaker 1: Contra Controversy. I can't speak today erin. It's a five
Speaker 1: part series.
Speaker 3: Check it out, good good stuff.
Speaker 5: You did a good job, I think thanks.
Speaker 3: I also had a.
Speaker 4: Number of papers for this episode, I think probably my
Speaker 4: three favorites that cover a lot of ground. One was
Speaker 4: from twenty twenty by Luo at All from Nature Reviews
Speaker 4: Molecular Cell Biology. It was called Mechanisms and Regulation of
Speaker 4: Cholesterol Homeostasis, so this is just like how our bodies
Speaker 4: are using cholesterol. There was another older one by Maxfield
Speaker 4: and Tabas from two thousand and five in Nature called
Speaker 4: Roll of Cholesterol and Lipid Organization in Disease. And then
Speaker 4: one from twenty nineteen by Holmes and A. La Corpela
Speaker 4: from Nature Reviews Cardiology just titled what is LDL cholesterol?
Speaker 4: So that was a good one too. But they have
Speaker 4: a bunch more and you can check them all out
Speaker 4: from like these ones from this episode, but also from
Speaker 4: all of our other episodes on our website.
Speaker 5: This podcast with Killia dot Com I.
Speaker 3: Do the episodees tab.
Speaker 1: Indeed, thank you again so much, Tori for sharing your
Speaker 1: story with us. It means a lot, it really does.
Speaker 5: Thank you.
Speaker 1: Thank you also to Bloodmobile for providing the music for
Speaker 1: this episode and all of our episodes.
Speaker 4: Thank you to Leanna and Tom and Mark and Jessica
Speaker 4: and Christine, everyone, everyone exactly right. Yes, we really appreciate
Speaker 4: everything that you do for us.
Speaker 1: We do. Thank you to you listeners for listening, watchers
Speaker 1: for watching. Anyone who subscribes, participates, does anything with this
Speaker 1: podcast interacts in any way, We truly appreciate it.
Speaker 4: We do. Thank you, and as always, a special shout
Speaker 4: out to our patrons for your support over on Patreon.
Speaker 4: It means so much to us. Truly, thank you, truly.
Speaker 3: Thank you.
Speaker 1: Until next time, wash your hands, you filthy animals.